Clinical Trials Register

Summary
EudraCT Number:	2021-001672-42
Sponsor's Protocol Code Number:	0627-19
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2021-03-26
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2021-001672-42

A.3

Full title of the trial

A Multicentre, Open Label, Balanced, Randomized, Single-Dose, Two-Stage, Two-Treatment, Two-Period, Two-Sequence, Two-Way, Cross-Over Study To Evaluate Comparative Bioavailability Of Temozolomide Powder For Oral Suspension, 300 Mg/15 Ml (Test Drug) With Temodal® Capsules 250 mg (Reference Drug) In Patients Of Malignant Gliomas Under-Going Treatment With Temozolomide Under Fasting Conditions

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Comparative Bioavailability study of two products of Temozolomide in Patients of Malignant Gliomas Under-Going Treatment with Temozolomide under Fasting Conditions

A.4.1

Sponsor's protocol code number

0627-19

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/147/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Intas Pharmaceuticals Ltd
B.1.3.4	Country	India
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Intas Pharmaceuticals Ltd.
B.4.2	Country	India
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Intas Pharmaceuticals Ltd.
B.5.2	Functional name of contact point	Mr. Kavan Pandya
B.5.3	Address:
B.5.3.1	Street Address	Corporate House, Nr. Sola Bridge, S.G. Highway, Thaltej
B.5.3.2	Town/ city	Ahmedabad
B.5.3.3	Post code	380054
B.5.3.4	Country	India
B.5.4	Telephone number	917939837000
B.5.5	Fax number	917926578862
B.5.6	E-mail	kavan_pandya@intaspharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Temozolomide oral Suspension 300 mg/15 ml
D.3.4	Pharmaceutical form	Powder for oral suspension
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TEMOZOLOMIDE
D.3.9.1	CAS number	85622-93-1
D.3.9.3	Other descriptive name	TEMOZOLOMIDE
D.3.9.4	EV Substance Code	SUB10889MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Temodal® (Temozolomide) capsule 250 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TEMOZOLOMIDE
D.3.9.1	CAS number	85622-93-1
D.3.9.3	Other descriptive name	TEMOZOLOMIDE
D.3.9.4	EV Substance Code	SUB10889MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients of malignant gliomas under-going treatment with temozolomide under fasting conditions

E.1.1.1

Medical condition in easily understood language

Patients of Malignant Gliomas

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029205
E.1.2	Term	Nervous system disorders
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To characterize the pharmacokinetic profile and to compare bioavailability of test formulation with reference formulation

E.2.2

Secondary objectives of the trial

To monitor the safety of the patients, who are exposed to the
investigational medicinal products.

To evaluate taste/palatability of the sponsor's test product.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or Female patients between 18-70 years of age (Both Inclusive).
2. Patients and/or LAR must be able to understand the investigational nature of this study and to give written informed consent prior to the participation in the trial.
3. Patient with documented evidence of one of the following
a. Newly-diagnosed glioblastoma multiforme during monotherapy phase who are already receiving or are about to start receiving temozolomide 250 mg once daily as their calculated individualized dose (e.g. based upon factors such as tumor type, body surface area, cycle number and toxicity)
b. With malignant gliomas, such as glioblastoma multiforme or anaplastic
astrocytoma ((anaplastic oligodendrogliomas and anaplastic oligoastrocytomas,
and some less common tumours such as anaplastic ependymomas and anaplastic gangliogliomas) showing recurrence or progression after standard therapy and requiring above stated dosing.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5. Body mass index 18 to 30 kg/m2 (both inclusive) with minimum weight being 45 kg
6. Patients with adequate cardiac function defined as left ventricular ejection fraction [LVEF] ≥50% and no other clinically significant findings on ECHO
7. Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
8. At least 4 weeks must have elapsed between the last day of
radiotherapy and date of randomization
9. Patients with life expectancy of at least 3 months.
10. Able to comply with study requirement in opinion of Investigator.
11. Adequate hematologic status, Renal and Liver function.
12. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of minor surgery; at least 4 weeks must have elapsed from the time of major surgery
13. Male patients must agree to use an effective contraceptive method
throughout the study and for 6 month after last dose of Temozolomide
14. Females of reproductive potential (which include girls who have entered puberty and all women who have a uterus and ovaries and have not completed menopause), must use an acceptable and effective method of avoiding pregnancy, starting from the first dose of study drug until the end of study. Cessation of birth control after this point should be discussed with a responsible physician. For this study, acceptable and effective methods of contraception include: -Tubal sterilization (tubal ligation performed more than one month
before Study
Day 1; transcervical tubal occlusion procedure performed more than six months
before Study Day 1)
-Intrauterine Device (IUD)
-Progestin implant (i.e. Implanon or its equivalent)
-Progestin injection or progestin oral contraceptive pill plus one barrier
method (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide,
female condom, or male condom)
-Two barrier methods used together (cervical cap, diaphragm,
contraceptive sponge, or vaginal spermicide plus a male or female condom)
-Absolute sexual abstinence (no sexual intercourse or genital contact
with a male partner).
In case of postmenopausal females (Menopause is the permanent end of menstruation and fertility), menopause should be clinically
confirmed by a patient's healthcare provider. Females who have 12 consecutive months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy), need not use the contraceptive measures specified above for females of reproductive potential. The investigator should ensure that the patient is using an effective method of avoiding pregnancy as per protocol.

E.4

Principal exclusion criteria

1. Pregnant or breast-feeding female.
2. Known hypersensitivity to Temozolomide, Dacarbazine or any other ingredients of the formulation
3. Patient in need of receiving the study medication via nasogastric tube
4. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
5. Active or history of opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P. carinii or other microorganism if under treatment with myelotoxic drugs.
6. Patients with severe hepatic impairment (Child pugh class C) or with
renal impairment.
7. Use of any recreational drugs (cocaine, amphetamines, barbiturates,
benzodiazepines, cannabinoids and morphine) or history of drug or alcohol addiction
8. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
9. Other serious illness or medical condition that would prohibit the understanding and giving of informed consent
10. A positive hepatitis screen including hepatitis B surface antigen or
HCV antibodies.
11. Patients tested positive for HIV and/or syphilis.
12. The receipt of an investigational product, or participation in a drug research study within a period of 30 days prior to the first dose of investigational Product (Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the study).
13. Any other condition/Abnormal baseline that, in the investigator's judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study
14. Donation / loss of blood (without replenishment) (1 unit or 350
mL) within 90 days prior to receiving the first dose of study medicine.
15. Uncontrolled hypertension (systolic blood pressure [BP] >140 or diastolic BP >90mm Hg) or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible).
16. Patients who are smokers or tobacco users in any form.
17. Patients of reproductive potential unwilling to use acceptable contraception (as defined in the protocol inclusion criteria).

E.5 End points

E.5.1

Primary end point(s)

To characterize the pharmacokinetic profile and to compare bioavailability of test formulation with reference formulation

E.5.1.1

Timepoint(s) of evaluation of this end point

Total 21 blood samples (each of 04 mL) will be collected from each
patient in each period.
The venous blood samples will be withdrawn at pre-dose (0.000
hour) and 0.083, 0.167, 0.333, 0.500, 0.750, 1.000, 1.250, 1.500,
1.750, 2.000, 2.500, 3.000, 3.500, 4.000, 5.000, 6.000, 7.000, 8.000,
10.000 and 12.000 hours following drug administration in each
period

E.5.2

Secondary end point(s)

To monitor the safety of the patients, who are exposed to the
investigational medicinal products.

To evaluate taste/palatability of the sponsor's test product.

E.5.2.1

Timepoint(s) of evaluation of this end point

Vital signs and body measurements-
At the time of the Dosing: Pre-dose, and at 4, 8 and 12 hr post dose. A deviation of 10 minutes will be allowed for vital assessment post dose. Pre dose vitals will be measured within 60 min prior to dosing.

Physical Examination: At every visit (on the day of dosing, it will be
performed before dosing in each period)

Hematology; Blood chemistry; Urinalysis (at Clinical Lab): Screening
and at the end of the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

Yes

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

India

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial will be the date of the last scheduled procedure shown in the Schedule of Activities for the last participant in the study

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Not Applicable

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Erode Cancer Centre Private Ltd, Erode
G.4.3.4	Network Country	India
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	HCG Manavata Cancer Centre, Nashik
G.4.3.4	Network Country	India
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Kiran Hospital MultiSuper Speciality Hospital & Research Centre, Surat
G.4.3.4	Network Country	India
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	Vydehi Institute of Medical Sciences &Research Centre, Bangalore
G.4.3.4	Network Country	India
G.4 Investigator Network to be involved in the Trial: 5
G.4.1	Name of Organisation	Sujan Surgical Cancer Hospital And Amravati Cancer Foundation, Amravati
G.4.3.4	Network Country	India
G.4 Investigator Network to be involved in the Trial: 6
G.4.1	Name of Organisation	Rajalakshmi Memorial Hospital, Chennai
G.4.3.4	Network Country	India
G.4 Investigator Network to be involved in the Trial: 7
G.4.1	Name of Organisation	KLES’ Dr. Prabhakar Kore Hospital & Medical Research Centre, Belagavi
G.4.3.4	Network Country	India

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	India

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